1. Field of the Invention
The present invention relates to novel fluorinated benzoyl compounds useful as intermediates for medicines and agricultural chemicals, particularly as intermediates for fluorinated pyridone carboxylic acid type synthetic antibacterial agents.
2. Discussion of the Background
It is known that 1,4-dihydro-4-oxoquinoline derivatives having a cyclopropyl or a substituted aryl group at the 1-position (hereinafter referred to as quinolone compounds) are useful as fluorine-containing synthetic antibacterial agents. As intermediates for the synthesis of such antibacterial agents, the following intermediates have been proposed.
(1) Japanese Unexamined Patent publication No. 74638/1983 discloses a synthesis of a quinolone compound having a cyclopropyl group at the 1-position and the intermediates for the synthesis thereof. ##STR3##
(2) Japanese Unexamined Patent Publication No. 85350/1986 discloses a synthesis of a quinolone compound via 2,4-dichloro-5-fluorobenzoic acid from 1,3-dichloro-4-fluorobenzene as the starting material. ##STR4##
(3) Japanese Unexamined Patent Publication No. 148484/1987 discloses a synthesis of a quinolone compound having a thienyl group at the 1-position from 2-bromo-4,5-difluorobenzoic acid. ##STR5##
In both processes disclosed in publications (1) and (2), 7-chloroquinolone compounds are prepared via 2,4-dichloro-5-fluorobenzoic acid. Such 7-chloroquinolone compounds are reacted, usually after the hydrolysis, with a cyclic amine for conversion to various synthetic antibacterial agents, as shown below. ##STR6## wherein R.sup.2 is cyclopropyl, a substituted aryl group or a thienyl group.
However, the reactivity of chlorine at the 7-position of this quinolone compound derived from the chlorine at the 4-position of 2,4-dichloro-5-fluorobenzoic acid is not high, and there is a drawback that the yield is inadequate, or the reaction condition is obliged to be severe even when the cyclic amine is a usual compound such as piperazine or a substituted piperazine.
Further, in the case of an amine compound having a low reactivity such as a tricyclic diazabicyclo alkyl compound as disclosed in Japanese Unexamined Patent Publication No. 103083/1987, it is preferred to employ highly reactive 7-fluoroquinolone compounds instead of the 7-chloroquinolone compounds having low reactivities.
The reactions of the 6,7-difluoroquinolone compound derived from 2-bromo-4,5-difluorobenzoic acid as shown in publication (3) with the cyclic amines proceed in good yield. However, this process has a drawback that 2-bromo-4,5-difluorobenzoic acid used as an intermediate in this process is difficult to synthesize. Namely, as a synthesis of 2-bromo-4,5-difluorobenzoic acid, Japanese Unexamined Patent Publication No. 108839/1987 discloses a hydrolysis method of 2-bromo-4,5-difluorobenzotrifluoride. However, by this method, 3,4-difluorobenzotrifluoride used as the starting material is hardly available and is difficult to synthesize. Further, this method has an additional disadvantage that an expensive corrosion-resistant material is required for the apparatus for the hydrolysis reaction.
Further, it is possible to obtain 2-bromo-4,5-difluorobenzoic acid by using known reactions, as shown below. ##STR7##
However, this method requires expensive 3,4-difluoroaniline as a starting material and employs highly toxic and dangerous copper cyanide. Therefore, it is difficult to practically operate this method on an industrial scale.
On the other hand, Japanese Unexamined Patent Publication No. 108839/1987 discloses a process represented by the following reaction as the only method for the production of 2-chloro-4,5-difluorobenzoic acid. ##STR8##
However, this process generates hydrogen fluoride, and accordingly has a drawback that the material of the reactor is obliged to be expensive such being disadvantageous for industrial operation.